Citations

Introduction: The efficacy and safety of novel oral anticoagulants (NOACs) has not been assessed in subjects with renal impairment. Methods: We performed a meta-analysis of RCTs comparing NOACs with warfarin in patients with atrial fibrillation (AF), in relation to renal function estimated by glomerular filtration rate (GFR): normal (GFR>80 ml/min/1.73m2), mild (50-80 mL/min/1.73m2), and moderate (<50 mL/min/1.73m2) impairment. MEDLINE, Embase, Web of Science and the Cochrane Library were searched to identify articles published up to the third week of January 2015. Data were supplemented with FDA data. Data on stroke or systemic embolism (S/SE) and major bleeding according to renal function were collected and extracted. We estimated the pooled relative risk (RR) of S/SE and major bleeding, for NOACs compared to warfarin. Results: We retrieved four randomized clinical trials (each randomizing dabigatran, rivaroxaban, apixaban, or endoxaban versus warfarin) enrolling a total of 58338 subjects, 29123 randomized to NOACs and 29123 randomized to warfarin; 21132 had normal renal function, 13126 had mild and 11027 had moderate renal impairment. In subjects with moderate renal impairment, compared to warfarin, NOACs reduced the risk of S/SE (RR 0.8; 95% CI 0.68-0.94) and major bleeding (RR 0.80; 95% CI 0.71-0.91). In subjects with mild renal impairment NOACs were associated with a reduced risk of S/SE (RR 0.75; 95% CI 0.66-0.85) and major bleeding (RR 0.87; 95% CI 0.79-0.95). In subjects with normal renal function no difference in the risk of S/SE was observed, while the risk of major bleeding was slightly less for subjects taking NOACs (RR 0.87; 95% CI 0.76-0.99). The test for interaction among groups of renal function was borderline significant for S/SE, but not for major bleeding. Conclusions: The use of NOACs was associated with a reduced risk of S/SE in subjects with mild or moderate renal impairment; while the risk of bleeding was reduced by NOACs compared to warfarin.

Abstract Pulsed electric fields (PEFs) have emerged as an ideal cardiac ablation modality. At present numerous clinical trials in humans are exploring PEF as an ablation strategy for both atrial and ventricular arrhythmias, with early data showing significant promise. As this is a relatively new technology there is limited understanding of its principles and biophysics. Importantly, PEF biophysics and principles are starkly different to current energy modalities (radiofrequency and cryoballoon). Given the relatively novel nature of PEFs, this review aims to provide an understanding of the principles and biophysics of PEF ablation. The goal is to enhance academic research and ultimately enable optimization of ablation parameters to maximize procedure success and minimize risk.

Background: Rigorous study of ventricular fibrillation (VF) is not feasible in humans. The spatiotemporal characteristics of prolonged VF remain undefined, limiting our understanding of this lethal rhythm. Methods: VF was mapped in 4 canines. The endocardial and epicardial left ventricle (LV) and right ventricle (RV) were sequentially mapped at 0 to 15, 15 to 30, 30 to 45, and 45 to 60 minutes post-induction. Ten consecutive beats were used to determine the average cycle length and regularity index of ventricular and His-Purkinje system signals in discrete regions during each time interval. Results: Average VF time was 58±12 minutes. The shortest ventricular cycle length was present in the RV apical region (70±10 msec) at 0 to 15 minutes and at 15 to 30 minutes (89±31 msec) and LV apical region at 45 to 60 minutes (242±163 msec). The His-Purkinje system cycle length was the shortest at the RV outflow tract (75±3 msec) at 0 to 15 minutes, RV inflow and free wall (89±12 msec) at 15 to 30 minutes, LV apical region (83±14 msec) at 30 to 45 minutes, and inferior and inferolateral LV (145±23 msec) at 45 to 60 minutes. Regularity index was the highest in the RV inflow and free wall (78%) at 0 to 15 minutes, RV apical region (86%) at 15 to 30 minutes, LV septum and epicardial anterior RV (80%) at 30 to 45 minutes, and anterior and anterolateral LV (75%) at 45 to 60 minutes. Conclusions: These data suggest significant regional changes in electrical activity throughout VF in canines. A transition of fastest electrical activity from RV to LV apical regions across VF was observed. These novel insights of the temporal and spatial changes of VF merit further evaluation in diseased hearts to assess for reproducibility of findings.

Introduction: Clinical predictive value of transient prolonged ventricular conduction and repolarization during right ventricular (RV) pacing have not been studied. Hypothesis: Ventricular conduction and repolarization prolongation during RV pacing predict risk of arrhythmic and mortality events. Methods: Electrophysiology studies in 501 patients with cardiomyopathy (CM) were reviewed. Duration changes of QRS and QT interval during pacing from the RV apex were measured. Subjects were followed up for a mean of 3.2 years for arrhythmic events and total mortality. Results: Participants had a mean age 65 yrs, 80% male, 74% funcional class II or III, and a mean EF of 33.1%. A paced QRS duration > 190 ms was associated with more severe CM and in multi-variable analysis it was associated with a 3.5 times higher risk of ventricular arrhythmias or appropriate defibrillator therapy (HR 3.5, 95% CI 2.3-5.4, p<0.01) and 2.6 times higher risk of total mortality or arrhythmic events (HR 2.6, 95% CI 2.3-3.4, p<0.01) compared to a paced QRS duration <190 ms, independent of baseline EF or baseline QRS duration, and after adjustment for electrophysiology study results, baseline functional class, type of cardiomyopathy and other relevant clinical factors. Similarly a QTc interval during RV pacing > 620 ms was associated with a 2.7 times higher risk of arrhythmic events compared to a QTc interval during RV pacing < 620 ms. Conclusions: Prolongation of ventricular conduction (QRS > 190 ms) and repolarization (QTc > 620 ms) observed during RV pacing in subjects with CM are associated with higher risk of arrhythmic events, defibrillator therapies and all-cause mortality.

Abstract Background Older adults with severe aortic stenosis (AS) are at high risk of mortality unless surgical or transcatheter aortic valve replacement (AVR) is performed. Risk stratification often becomes complicated in frail elders with multi-morbidity, and time constraints limit thorough evaluation of geriatric comorbidities in the outpatient clinic setting. Purpose Utilization of an automated administratively-derived electronic health record (EHR) tool may aid in risk stratification of AS patients undergoing AVR. Methods We reviewed patients with severe AS undergoing AVR at our hospital program and cross-referenced with the Elder Risk Assessment (ERA) score. The ERA score is an administratively abstracted score derived on adults &gt;60 years old followed by general medicine clinic. It contains the following variables: marital status, age, hospitalized days in preceding 2 years, diabetes, coronary disease, heart failure, stroke, pulmonary disease, cancer, and dementia; higher scores indicate greater risk for adverse outcomes. Kaplan-Meier method was used to estimate survival by ERA score tertile. Cox regression was used to test the association of ERA with survival. Results There were 97 patients with severe AS undergoing AVR with ERA scores. Mean age was 80.6 (±6.6) years, 37% were female, average Society of Thoracic Surgery (STS) score was 3.6% (± 2.6), and 7% had transcatheter AVR. Co-morbidities were prevalent and included atrial fibrillation (41%), chronic renal failure (16%), stroke (14%), and diabetes (35%). Over a mean follow-up of 68 months (± 37.9 months), there were 62 deaths. Elevated ERA score was associated with worse long term survival (p=0.016 by log-rank) (Figure 1), with only 49% surviving at 5 years in the highest ERA tertile vs 68% in the lowest ERA tertile. Cox regression demonstrated that the relative risk of death per 6 unit increase in ERA score was 1.54 (95% CI 1.21–1.96, P&lt;0.001) in single variable analysis and 1.43 (95% CI 1.11–1.84, P=0.006) after adjusting for STS score. Conclusions Patients undergoing AVR for severe AS are often co-morbid older adults. An automated EHR derived ERA score was independently associated with survival after accounting for STS score and may streamline and improve risk assessment in these patients. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Mayo Clinic

AbstractProviders should be aware of the possibility of cardiac resynchronization therapy‐related proarrhythmia which could be life‐threatening. His‐bundle pacing may serve as an alternative, more physiological, option in the management as it preserves the normal sequence of depolarization from the septum to the lateral wall, and from endocardium to epicardium.

AbstractBackgroundAtrial fibrillation (AF) among patients with heart failure with reduced ejection fraction (HFrEF) is associated with adverse clinical outcomes. Our primary aim was to evaluate patient‐centered outcomes and surrogate outcomes following catheter ablation (CA) of AF among patients with HFrEF compared to standard medical therapy with or without device therapy (atrioventricular node ablation and cardiac resynchronization therapy).MethodsA systematic literature review was performed limiting our searches to randomized control trials reporting outcomes of CA compared to standard medical therapy with or without device therapy were included. Patient‐centered outcomes were relative reduction in all‐cause mortality, heart failure readmissions, and recurrence of AF. Surrogate outcomes of interest were change in ejection fraction, change in peak oxygen consumption, reduction in brain natriuretic peptide levels, change in 6‐minute walk distance, and change in Minnesota living with heart failure score.ResultsSeven randomized control trials (Patient n = 721) met our inclusion criteria. All trials used radiofrequency energy for CA of AF. CA for AF was associated with significantly lower all‐cause mortality (Risk ratio [RR] = 0.52, 95% confidence interval [CI] = 0.35‐0.76, P = 0.001, I2 = 0%), lower rate of heart failure readmission (RR = 0.58, 95% CI = 0.46‐0.74, P < 0.001, I2 = 0%) and lower rate of AF recurrence (RR = 0.33, 95% CI = 0.22‐0.50, P < 0.001, I2 = 68%) as compared to standard medical therapy. Surrogate outcomes showed a similar benefit favoring CA.Conclusion and RelevanceCatheter ablation for AF in HFrEF is associated with improvement in patient‐centered outcomes and surrogate outcomes when compared to standard medical therapy with or without device therapy.

AbstractBackgroundCardiac resynchronization therapy (CRT) reverses left ventricular remodeling and improves left ventricular systolic function. However, little is known about whether CRT improves ventricular conduction.ObjectiveTo determine the relationship between CRT response and QRS narrowing.MethodsThe study included consecutive patients who underwent CRT with defibrillator (CRT‐D) implantation between January 2002 and December 2012 and had subsequent generator replacement (GR). At the time of GR, super‐responder was defined as those who had left ventricular ejection fraction (LVEF) of 50% or more; patients who had an LVEF of 36–49% with an increase of more than 5% were considered responders, and the others were nonresponders. All patients were assessed 6 months after CRT‐D implantation and at the time of GR.ResultsOf 114 study patients, 58 (50.9%) were nonresponders, 29 (25.4%) responders, and 27 (23.7%) super‐responders. QRS narrowing at 6 months was significant in super‐responders (175.4 ± 21.4 to 159.7 ± 20.7 ms, P = 0.001) and responders (169.0 ± 21.3 to 157.7 ± 17.6 ms, P = 0.008). At time of GR, only super‐responders had further QRS narrowing (159.7 ± 20.7 to 146.3 ± 19.2 ms, P < 0.001). QRS duration change after 6 months was independently associated with super‐response (hazard ratio: 1.20 for every 5 ms QRS duration narrowing; 95% confidence interval, 1.06–1.38; P = 0.005), and QRS narrowing of 10 ms or more was associated with lower risk of all‐cause mortality after GR.ConclusionContinuous QRS narrowing after CRT, as an electrical marker, is associated with a super‐response to CRT. Further QRS narrowing 6 months after CRT implantation was associated with lower risk of mortality after GR.